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Written1998-10Dietmar R Lohmann
Institut fuer Humangenetik, Hufelandstr. 55, D-45122 Essen, Germany

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1. Identity

Atlas_Id 10031
Genes implicated inRB1 
Inheritance predisposition to retinoblastoma is transmitted as an autosomal dominant trait; it is caused by mutations in the RB1 gene; penetrance and expressivity depend on the nature of the predisposing mutational change; there is also a non-hereditary form of retinoblastoma (mostly in children with isolated unilateral retinoblastoma) that is caused by RB1-mutations confined to somatic cells

2. Clinics

Phenotype and clinics
  • retinoblastoma in early childhood: white reflexes in one or both eyes or strabismus usually are the first signs indicating this malignant eye tumour; in most children with the hereditary retinoblastoma, both eyes are affected by multiple tumour foci (bilateral multifocal retinoblastoma)
  • adults (most often relatives of patients with retinoblastoma) may show retinal scars indicating regressed (non-progressive tumours).
  • in addition to retinoblastoma, children with cytogenetic deletions involving 13q14 may show developmental delay and dysmorphic signs.
  • Neoplastic risk early childhood: formation of retinoblastomas (see genotype-phenotype correlation)
    adolescence and adulthood: tumours outside the eye (second primary neoplasms):
  • osteosarcoma,
  • melanoma,
  • brain tumours (pinealoma in particular some patients also show multiple benign tumours of adipose tissue (lipoma).
  • Treatment retinoblastomas can be cured by (depending on size and location): local therapy (photocoagulation, cryotherapy, radiation), combined systemic and local therapy, or enucleation of the eye; surveillance : following the diagnosis of retinoblastoma, repeated examinations under general anesthesia are required for early diagnosis of new tumour foci; up to now, no screening for second primary neoplasms.
    Prognosis most often, treatment of retinoblastoma is very effective and, therefore, death from retinoblastoma is rare; however, life span in patients that develop second primary neoplasms is reduced (cumulative mortality at age 40: 6.4% in bilateral patients without radiotherapy, 1.5% in patients with unilateral retinoblastoma).

    3. Genes involved and Proteins

    Gene NameRB1 (retinoblastoma)
    Location 13q14.2
    Description 180 kb genomic DNA containing 27 exons
    Transcription 4.7 kb mRNA with 2.7 kb open reading frame
    Description 928 aa nuclear phosphoprotein
    Localisation nucleus
    Function involved in cell cycle regulation
  • mutations predisposing to retinoblastoma are one allele mutations; in retinoblastoma, both copies of the RB1 gene are mutated (two-step inactivation mechanism typical of tumor suppressor genes).
  • nature and localization of individual mutations are heterogeneous regarding their nature : 20% deletions larger 1kb; 30% small deletions or insertions; 45% point mutations.
  • and location : mutations have been found in 25 of the 27 coding exons and in promoter elements.
  • Genotype-phenotype correlation : most mutant RB1-alleles show premature termination codons; typically, these mutant alleles are associated with almost complete penetrance (>95%) and high expressivity (more than 6 individual retinoblastoma foci per individual and, therefore, most often involvement of both eyes); some rare mutant alleles that code for proteins with retention of parts of the functions of the wild-type prote in or that result in diminished amounts of wild-type transcript are associated with incomplete penetrance (

  • 4. Bibliography

    Presenting signs of retinoblastoma.
    Abramson DH, Frank CM, Susman M, Whalen MP, Dunkel IJ, Boyd NW 3rd
    The Journal of pediatrics. 1998 ; 132 (3 Pt 1) : 505-508.
    PMID 9544909
    Molecular etiology of low-penetrance retinoblastoma in two pedigrees.
    Dryja TP, Rapaport J, McGee TL, Nork TM, Schwartz TL
    American journal of human genetics. 1993 ; 52 (6) : 1122-1128.
    PMID 8099255
    Mortality from second tumors among long-term survivors of retinoblastoma.
    Eng C, Li FP, Abramson DH, Ellsworth RM, Wong FL, Goldman MB, Seddon J, Tarbell N, Boice JD Jr
    Journal of the National Cancer Institute. 1993 ; 85 (14) : 1121-1128.
    PMID 8320741
    Mutations in the ligand-binding domain of the kit receptor: an uncommon site in human piebaldism.
    Fleischman RA, Gallardo T, Mi X
    The Journal of investigative dermatology. 1996 ; 107 (5) : 703-706.
    PMID 8875953
    A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma.
    Friend SH, Bernards R, Rogelj S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP
    Nature. 1986 ; 323 (6089) : 643-646.
    PMID 2877398
    Chemotherapy with focal therapy can cure intraocular retinoblastoma without radiotherapy.
    Gallie BL, Budning A, DeBoer G, Thiessen JJ, Koren G, Verjee Z, Ling V, Chan HS
    Archives of ophthalmology. 1996 ; 114 (11) : 1321-1328.
    PMID 8906022
    Retinoma: spontaneous regression of retinoblastoma or benign manifestation of the mutation?
    Gallie BL, Ellsworth RM, Abramson DH, Phillips RA
    British journal of cancer. 1982 ; 45 (4) : 513-521.
    PMID 7073943
    A simplified scheme for genetic counseling in retinoblastoma.
    Musarella MA, Gallie BL
    Journal of pediatric ophthalmology and strabismus. 1987 ; 24 (3) : 124-125.
    PMID 3598831
    Oncogenic germ-line mutations in Sp1 and ATF sites in the human retinoblastoma gene.
    Sakai T, Ohtani N, McGee TL, Robbins PD, Dryja TP
    Nature. 1991 ; 353 (6339) : 83-86.
    PMID 1881452
    Frequency of somatic and germ-line mosaicism in retinoblastoma: implications for genetic counseling.
    Sippel KC, Fraioli RE, Smith GD, Schalkoff ME, Sutherland J, Gallie BL, Dryja TP
    American journal of human genetics. 1998 ; 62 (3) : 610-619.
    PMID 9497263
    Complete genomic sequence of the human retinoblastoma susceptibility gene.
    Toguchida J, McGee TL, Paterson JC, Eagle JR, Tucker S, Yandell DW, Dryja TP
    Genomics. 1993 ; 17 (3) : 535-543.
    PMID 7902321

    5. Citation

    This paper should be referenced as such :
    Lohmann, DR
    Atlas Genet Cytogenet Oncol Haematol. 1999;3(1):48-49.
    Free journal version : [ pdf ]   [ DOI ]
    On line version :

    6. External links

    Other databaseDatabase of RB1-gene mutations
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed

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